Anti-osteosarcoma property of decorin-modified titanium surface: A novel strategy to inhibit oncogenic potential of osteosarcoma cells

Biomed Pharmacother. 2020 May:125:110034. doi: 10.1016/j.biopha.2020.110034. Epub 2020 Feb 25.

Abstract

Osteosarcoma is the most common bone sarcoma in adolescents. Decorin (DCN) has been proposed to be a new anti-osteosarcoma therapeutic strategy. Our previous study has loaded decorin on titanium (Ti) surface by polydopamine (DOPA) as an anchor to enhance osseointegration. In this study, we investigated the effect of decorin-coated Ti substrates (TI-DOPA-DCN) on the oncogenic potential of osteosarcoma cells SAOS-2. The substrates were placed in 24-well plates for cell culture. Cell viability was determined by Cell Counting Kit-8 (CCK8) assay. Apoptosis was evaluated by DAPI staining and Annexin V-FITC/PI double staining analysis. Cell cycle was analyzed by flow cytometry. Cell migration and invasion were evaluated by Transwell assay. For co-culture, the pre-osteogenic cells MEC3T3-E1 and osteosarcoma cells SAOS-2 were stained with cell membrane fluorescent dyes, and then mixed (1:1) for co-culture. The cells were observed under a fluorescence microscope at four time points of 24, 48, 72, and 96 h. The results showed that TI-DOPA-DCN substrate can selectively inhibit cell proliferation of osteosarcoma cells but not pre-osteoblasts. However, the cell cycle of SAOS-2 was not affected by TI-DOPA-DCN substrates. Both DAPI staining and Annexin V-FITC/PI double staining analysis revealed that TI-DOPA-DCN substrates induced apoptosis of osteosarcoma cells. Transwell assay showed that TI-DOPA-DCN substrates inhibited invasion and migration of osteosarcoma cells. Moreover, TI-DOPA-DCN substrates inhibited the growth of osteosarcoma cells but promoted that of pre-osteoblasts in the coculture system. Taken together, these findings suggested that decorin coating on Ti surface simultaneously inhibited the oncogenic potential of osteosarcoma cells but enhanced cell growth of pre-osteoblasts, which could be applied to surface modification of Ti orthopedic implant.

Keywords: Anti-osteosarcoma; Decorin; Osteosarcoma; Surface modification; Titanium.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Coculture Techniques
  • Decorin / administration & dosage
  • Decorin / pharmacology*
  • Humans
  • Indoles / chemistry
  • Mice
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Polymers / chemistry
  • Time Factors
  • Titanium / chemistry*

Substances

  • Decorin
  • Indoles
  • Polymers
  • polydopamine
  • Titanium